Prokineticins (PK1 and PK2) are secreted, multifunctional chemokine-like peptides. Prokineticins exert their biological functions through the interaction with two G-protein coupled receptors (GPCRs) referred to as prokineticin receptor 1 (PROKR1 or PKR1) and prokineticin receptor 2 (PROKR2 or PKR2). PROKR1 and PROKR2 share approximately 87% overall amino acid sequence identity with one another. PK1 and PK2 each interact with PROKR1 and PROKR2. At the cellular level, activation of prokineticin receptors leads to calcium mobilization, stimulation of phosphoinositide turnover and activation of the MAP kinase signaling pathway. At the multicellular level, prokineticins exhibit angiogenic activity and induce cell proliferation and migration. Prokineticins and their receptors are associated with the development of several human cancers and have also been shown to participate in nociception and the transmission of pain. (See, e.g., Monnier and Samson, 2010, Cancer Letters 296:144-149; and Negri et al., 2009, Int. Rev. Neurobiol. 85:145-157).
The prokineticin signaling system represents a potential target for the treatment and/or prevention of a variety of diseases and disorders. Accordingly, a need exists in the art for novel therapeutic agents which target and modulate one or more components of the prokineticin signaling pathway, such as the prokineticin receptors (PROKR1 and PROKR2).